Principles of the molecular construction of multienzyme templates for peptide biosynthesis in integrated reaction sequences.

The amino acid sequences of the genes coding for four multienzyme peptide synthetases, operating by the thiotemplate mechanism are compared, to show underlying principles in the biosynthetic mechanism. Alignment with other carboxylic acid activating enzymes shows the sequences. LAY(V/I)I(Y/F)TSGT(T/S)GxPKGV and GELx(L/I)GGxG(V/I) to be involved in MgATP2-binding and adenylate formation, and two other sequences, one containing the element FxLGG(H/D)S(I/L) to be involved in covalent binding of the amino acid. As a general rule, 1000 amino acid building blocks are responsible for the incorporation of one amino acid into the nascent peptide.